HIV infection of children usually results in more rapid and severe disease than is seen in adults To explore the pathogenesis of pediatric AIDS we examined 20 rhesus macaques inoculated intravenously with SIV within 24 hours of birth Viral inocula included the pathogenic molecular clone SIVmac239 (n = 13), the macrophage-competent derivative SIVmac239/316 (n = 2), the minimally pathogenic SIVmac239 nef (n = 2) and uncloned SIVmac251 (n = 3) Infected neonates were sacrificed at intervals over the first 50 days (n = 16) or allowed to progress to terminal disease (n =4) Neonates inoculated with these viruses had higher viral loads than older animals inoculated with the same dose and stock of virus although differences did not reach statistical significance The highest viral loads were present in animals infected with SIVmac239 followed in order by SIVmac251, SIVmac239/316 and SIVmac239 nef The latter, were the only group of animals that showed normal weight gai n By in situ hybridization (ISH) virus was detectable in lymphoid tissues of all animals as early as 3 days postinoculation (dpi) with maximal numbers of infected cells by 14 dpi coincident with peak viremia The majority of infected cells were present in the T-cell zones of the spleen and lymph nodes and in the thymic medulla Rare, SIV-infected cells undergoing mitosis were also observed Combined in situ hybridization/immunohistochemistry experiments revealed that most of the infected cells were T-cells with little evidence of monocyte/macrophage infection Neonates infected with SIVmac239 nef had far fewer infected cells and they were primarily within germinal centers of the spleen and lymph nodes Histologically, spleen and lymph nodes of animals infected with SIVmac239 and SIVmac251 for < 50 days were characterized by an absence of follicular hyperplasia This is in contrast to older animals inoculated with these same viruses and age-matched neonates inoculated with eithe r SIVmac239/316 or SIVmac239 nef which had marked follicular hyperplasia and dysplasia In summary, while viral loads were not significantly different between neonates and older animals inoculated with the same stock and dose of virus, numerous other differences were observed that must be the result of age-specific host determinants